Background: The dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities. Method: A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100 mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan + cognitive behavioral therapy (CBT); or ClinMan + CBT + voucher-based reinforcement therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100 mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-min nurse-delivered ClinMan sessions. Weekly, 1-h CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models. Results: Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations. Conclusion: This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment.
Bibliographical noteFunding Information:
Role of funding source : Funding for this study was provided by the National Institute on Drug Abuse (NIDA) Medications Development Center Grant (P50-DA–9262). The NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Mooney is supported by a NIDA Career Development award K01-DA-019446. Dr. Moeller is supported by a NIDA Independent Scientist award K02-DA00403.
- Cocaine treatment
- Contingency management
- Voucher-based reinforcement therapy